Current Pediatric Research

Abstract

Mercury is a ubiquitous environmental pollutant with diverse adverse health effects that could result in death. Children are the most susceptible population of the world to mercury poisoning. Two earlier reviews by the author dealt with fatal mercury poisoning cases in the general population and mercury vapor exposure in dentistry. The objective of the present article is to review global studies on environmental mercury poisoning of children and get perspective on its impact on pediatric health by assessing the progress made in diagnosis, treatment, prevention and monitoring of the adverse effects. With the aid of several search platforms, studies of environmental mercury exposures in children published in the world literature were collected. With emphasis on clinical studies, details of the reported adverse health effects and treatments used were compiled along with prevention and monitoring aspects of mercury exposures. Mercury poisoning events were categorized based on exposure sites (at home or outside), its form (elemental, organic or inorganic), route (inhalation, oral ingestion, skin absorption or pre-and postnatal), duration (acute or chronic) and dose. The clinical signs, symptoms and treatments used in each category were separately enumerated for comparative purpose. Home is the most common site for children’s exposure to mercury attributable to breakage of fever thermometers, dental amalgam fillings, tainted cosmetics, toys and jewelry, and consumption of contaminated fish, OTC and herbal medicines, and dietary supplements. The main organs affected are brain, lungs, kidneys and immune systems. Clinical interpretation of blood and urine levels of mercury are unambiguous when they are high and become difficult as they approach normal range. While diagnosing mercury poisoning can be challenging, it can be made with reasonable reliability and promptly treated with chelation therapy. With the development of mercury-free products and manufacturing processes along with industrial pollution abatement measures, children’s exposure to mercury is currently being reduced. Parents, pediatricians, and school science teachers can play a major role in preventing mercury poisoning of children. This review should be of immediate interest to environmental scientists and regulators around the world.

Keywords

Mercury, Environment, Children’s Health, Diagnosis, Prevention, Monitoring.

Abbreviations

AA: Arachidonic Acid: AAP: American Academy Of Pediatrics; ADHD: Attention Deficit Hyperactivity Disorder; AHRQ: Agency For Healthcare Research And Quality (US); ASD: Autism Spectrum Disorders; ASGM: Artisanal and Small-Scale Gold Mining; ATSDR: Agency for Toxic Substances and Disease Registry (US); BAEP: Brainstem Auditory Evoked Potential; BASC: Behavior Assessment System for Children; BBB, Blood-Brain Barrier; BSID: Baby Scales of Infant Development; CDC: Center for Disease Control and Prevention (US); CHD: Coronary Heart Disease; CNS: Central Nervous System; CPT: Continuous Performance Test; DHA: Docosahexaenoic Acid; DMPS: 2,3-Dimercapto-1-ropanesulfonate; DMSA: Dimercaptosuccinic Acid; DNA: Deoxyribonucleic Acid; EFSA: European Food Safety Authority; EPA: Environmental Protection Agency (US); ER: Emergency Room; EU: European Union; FAO: Food And Agricultural Organization (WHO); FDA: Food And Drug Administration (US); FLB: Fluorescent Light Bulb; FTT, Finger-Tapping Test; GDS, Gesell Developmental Schedules; GI, Gastrointestinal; GMDS, Griffiths Mental Development Scales; HVAC: Heating, Ventilation and Air Conditioning; LED: Light Emitting Diode; MDI: Mental Developmental Index; MeHg: Methylmercury; MRI: Magnetic Resonance Imaging; MSCA, McCarthy Scales Of Children’s Abilities; NHNE, National Health And Nutrition Examination (US); NIEHS, National Institute Of Environmental Health And Safety (US); NIH: National Institutes of Health (US); NIOSH: National Institute Of Occupational Safety And Health (US); NSA: National Science Foundation (US); OTC: Over-The-Counter; PDI: Psychomotor Developmental Index; PHS: Public Health Service US); PPVT: Peabody Picture Vocabulary Test; PUFAs; Polyunsaturated Saturated Fatty Acids; RFD: Reference Dose; RI: Risk Index; ROS: Reactive Oxygen Species; SACMEQ: Southern and Eastern African Consortium for Monitoring Educational Equality; SBIS: Stanford- Binet Intelligence Scale; Se: Selenium; SH: Sulfhydryl; TGMD: Test for Gross Motor Development; TMT: Trail Making Test; TWI: Tolerable Weekly Intake; UK: United Kingdom; UNFAO: United Nations Food and Agriculture Organization; US: United States (of America); VEP: Visual Evoked Potential; VER: Visual Evoked Response; VRM: Visual Recognition Memory; WHO: World Health Organization; WISC: Wechsler Intelligence Scale for Children and WRAVMA: Wide-Range Assessment of Visual Motor Abilities.

Introduction

Children are the most susceptible population of the world to environmental mercury poisoning. The two major routes of mercury exposure are inhalation of its vapor in the polluted air and consumption of fish and seafood contaminated with its organic form, MeHg. According to WHO [1], the ubiquitous and persistent nature of mercury and its compounds pose a threat for the healthy development of the world’s children. The Minamata Convention [2] and EU Science for Environmental Policy [3] are currently addressing pediatric health problems raised by the complicated life cycle of mercury in the global environment. Study of early-life exposure to mercury and later-life diseases is a priority of the developmental origins of health and disease program of the US NIEHS [4] and WHO [5]. Also, WHO and the UN Environmental Programme have initiated global monitoring of children’s exposure to mercury [6]. In recent years, notable progress has been made in curtailing exposure of children to this important environmental pollutant and monitoring the health of those exposed to it [7].

Mercury poisoning in the general population that resulted in death [8] and its vapor exposure in dental practice [9] were the subject of two earlier reviews by the author. The present review deals with pediatric mercury poisoning of children ≤ 18 yr. of age.

Historical perspective

Human exposure to mercury is due to its presence in the global environment from natural sources (69%) and continued human contributions (31%) from its industrial, commercial, medical and dental usages over the past 200+yr [10-19]. The earth’s crust contains 0.05 mg mercury/kg and the current estimate of global mercury emissions is 7,527 Mg/yr. [20]. In the bioenvironment, mercury is transformed by microorganisms (plankton) to MeHg [21] and bioaccumulated in small fish feeding on it [22]. MeHg is further biomagnified in large predatory fish and other marine mammals ingesting these small fish [23]. Human contribution to the present-day mercury in Arctic marine animals used as food is estimated to be 92.4% [24]. The Arctic populations have blood mercury levels among the highest in the world that are associated with adverse health outcomes across life stages (from neurodevelopment in infancy to CHD in adults) [25]. The climate-induced amplification of MeHg in predator fish is projected to reach 8% by 2100 [26].

Mercury-containing industrial discharges (in addition to the atmosphere), agricultural runoffs (containing mercury-based fertilizers and pesticides) and domestic sewage (with mercury from cosmetics, OTC drugs, etc.) are the major polluters of lake, river and other large bodies of water [27-29]. Socioeconomic and health consequences of mercury pollution, and medical benefits of reducing mercury exposure in humans are current issues of global interest [30-33].

Mercury is devoid of any known physiological benefit and its exposure in any form (elemental, organic or inorganic) is considered potentially toxic to humans [34,35]. However, a physiological role for Hg++ during phototropic growth of the purple non-sulfur bacteria has been recently reported [36].

Based on an estimated ambient air level of 10 ng/m³ mercury, its average daily intake in humans by inhalation is ~0.2 μg and from drinking water containing 0.5 μg mercury/L it is ~1 μg [37]. However, food is by far the largest contributor to human mercury exposure (2-20 μg/day) with fish and seafood being the major sources.

In the current global pandemic of corona virus disease 2019 caused by SARS-CoV-2 (COVID-19), reduction of mercury exposure may be considered as a potential tool for lowering vulnerability and severity of this deadly respiratory viral infection [38-41]. An unusual and paradoxical feature of the current COVID-19 pandemic is that children appear to be less severely affected by this virus than adults [42].

Children’s exposure to mercury

The common forms and sources of mercury relevant to pediatric exposure are:

1. Elemental mercury, usually as vapor from mercury spills [43,44], dental fillings [45], religious practices [46] and tainted toys and jewelry [11],

2. Organic mercury compounds, MeHg being the most common through consumption of contaminated fish and seafood [47-49],

3. Maternal use of inorganic mercury compounds, such as bromide and chloride salts in cosmetics, household products, herbal medicines and dietary supplements [50,51].

The form of mercury a child is exposed to has significant effect on its toxic manifestation since there are major differences in the body uptake, transport and disposition of the three common forms of the metal [8,34,52]. Often children are simultaneously exposed to different forms of mercury which are generally chronic in nature and adverse effects tend to be definitive at higher doses but subjective at trace levels [1,18].

In children, vital organs (such as lung, brain and kidney, and immune systems) are at critical stages of development and often targets of adverse effects of mercury exposure [22,53-55]. This could occur even before birth since mercury readily passes through the placenta and enters the developing fetus during gestation in exposed pregnant women [56,57].

AAP has provided information on children’s mercury exposure for practicing pediatricians [58] and the US EPA [59] has published guidelines to physicians in conducting mercury medical surveillance programs. Also, WHO guidance for identifying populations at risk from mercury exposure is available [60].

Alarmed by the reports of residual mercury vapor exposure of children in daycare centers and new condominiums which were converted from industrial buildings which used mercury and inadequately remediated, the US Congress in 2008 directed ATSDR and CDC to form the Mercury Workgroup to investigate such mercury exposure in children. In 2009, the Workgroup published a comprehensive report with the following conclusions [61]:

Children as a group are more sensitive to mercury vapor exposures in contaminated spaces and at higher risk than adult population. Since they breathe at a faster pace, have larger lung surface area relative to body mass than adults, and their shorter stature, crawling and play activities keep children’s breathing zone closer to contaminated floor. The duration of such exposure (acute or chronic) and concentration of mercury govern the severity of adverse effects.

While environmental mercury poisoning of children around the globe continues to be reported to-date, there appears to be no literature review of the topic over a decade.

Literature Review

According to the 2020 annual report by the American Association of Poison Control Centers in the US, 1,965 calls pertaining to mercury were received with 1,256 involving broken fever thermometers [62]. Accidental mercury poisoning of children continues to be of public health concern in the US and around the world [63-71]. The objective of this review is to assess the current status of global mercury poisoning of children, provide up-to-date information on how to diagnose and treat, and appraise preventive and monitoring methods. This should be of interest to environmental scientists and regulators as well as pediatricians, medical personnel in hospital emergency rooms and poison control centers. Also, the information gathered should be useful to first responders and school science teachers in educating parents and their children how to minimize mercury exposure.

A literature search on the topic of mercury poisoning (key words: environment, mercury, poisoning and children) was performed using PubMed, MEDLINE, Academia-Edu, Science Direct and Google Scholar search platforms. Clinical studies published through June, 2023 were the main focus of this review. Those deemed relevant were used to collect detailed data on where, how, and the form (elemental, organic or inorganic) and nature (acute or chronic) of mercury exposures reported in children. Also, children’s ages, biological samples used as biomarkers, clinical signs and symptoms of adverse effects, treatments and autopsy results (in the case of fatalities) were gathered. Available historical and chronological data on mercury poisoning were also compiled for possible extrapolation and its relevance to current events.

Results

Over 50,000 articles on the general topic of toxic effects of mercury exposures in children were available online. Of these, 534 were identified as relevant to this review objective and details of the reported exposure events were obtained. In general, the robust studies from Brazil, Canada, EU (primarily Scandinavia and Spain), UK and US were a salient part of this review. They were separated into various exposure categories based on different forms of mercury, common sites and sources of contaminations. Details of mercury concentrations in various biological and tissue samples used as biomarkers were collected. The reported clinical signs, symptoms and treatment of mercury poisoning was gathered under elemental, organic and inorganic forms of mercury.

In the US, EPA has recognized the following neurodevelopmental disorders in children attributable to environmental pollutants [72]: vision and hearing impairments, ADHD, learning and intellectual disabilities, ASD and cerebral palsy. Also, WHO recognizes the above disorders in evaluating health risk of environmental pollutants in exposed children [73].

From conception through adolescence, rapid growth and developmental processes occur in children which can be disrupted by exposure to mercury in the environment [1,22,53]. This occurs through: 1) maternal exposure, prenatally in the uterus and postnatally via breast milk, 2) inhalation, 3) oral ingestion and 4) skin contact.

Mercury affects the reproductive function of men as well as women [74]. During gestation, both elemental mercury and MeHg readily cross the placental barrier and accumulate in the fetus [75,76]. Mercury body burden of the mother is shared by her fetus and neonate which may result in larger exposure doses due to their lower body weights. Also, children consume more contaminated food and beverages for their body weight than adults. Overall, compared to adults, children have more years of future life and thus more time to develop chronic diseases that may take decades to manifest (lag time) after mercury exposure [76-80].

Inhaled elemental mercury vapor is readily absorbed in lungs (~80%) and crosses the BBB. In the brain, it is oxidized to inorganic mercury (Hg++) and bound to macromolecules (DNA, enzymes, proteins, etc.) via SH groups. However, elemental mercury is slowly absorbed through skin and little is absorbed in the GI tract when ingested orally. In contrast, organic MeHg is readily absorbed through skin contact as well as in the GI tract (90%-95%) when ingested and crosses the BBB, biotransformed to Hg++ by demethylation and bound to macromolecules in the brain [81-84]. On a cellular level, MeHg induces oxidative stress by elevating ROS [85]. Since inorganic mercury compounds are poorly absorbed by dermal and oral routes (~10%), and do not cross the BBB, the main site for their accumulation is the kidney [55].

Inhaled elemental mercury vapor is excreted from the body in the exhaled breath, sweat and urine. Ingested mercury in liquid form is excreted in the feces unchanged [86,87]. Also, oral MeHg exposure leads to its excretion in the feces as inorganic mercury, since the gut flora can demethylate MeHg and modify its absorption and bioavailability [82]. The half-lives of the three common forms of mercury for elimination from the body are: elemental mercury (58 d), inorganic mercury (30-60 d) and MeHg (70-80 d) [83].

Elemental mercury generally does not accumulate in food [88] and MeHg usually not present in drinking water [36,89]. Diet and nutritional status of children (see Figure 1) have major impact on mercury toxicity [1,86,90,91].

Figure 1: Graphical abstract highlighting the origin of children’s exposure to elemental mercury, its organic and inorganic compounds and modulatory effect of diet and nutrition on mercury toxicity.

Discussion

The following are common sites for exposure of children to elemental mercury, and its organic and inorganic compounds:

Mercury exposure at homes

Home is the most common site for children’s exposure to mercury. Such exposure occurs due to: 1) consumption of mercury contaminated fish and other dietary constituents, 2) breakage of mercury-containing devices, e.g., fever thermometer, 3) heating mercury during unauthorized smelting operation by parents to extract gold and silver, 4) cultural or religious ceremonial utilization of mercury, 5) household use of unregulated cosmetics, herbal medicines and dietary supplements, and 6) family members unknowingly tracking mercury home from workplace. Additionally, children bringing home mercury from school science laboratories and abandoned factories could lead to the toxic metal vapor exposures (See below Sections From acute exposure to high doses of mercury and Mercury exposure at other locations, respectively).

From consumption of MeHg contaminated fish by mothers

Pregnant mothers who consume contaminated fish expose their offsprings to mercury during gestation and postnatally, through breastfeeding [48,49,92-94]. Mothers with lower body weight (<60 kg or ~132 lb) generally have higher mercury levels in their breast milk [95]. Extended breastfeeding (up to 3 yr.) is not significantly associated with elevated mercury level in children as measured in their scalp hair [96]. Interestingly, human breast milk contains mercury 8x WHO guideline amount for drinking water (1 μg/L), 4x that allowed in bottled water (2 μg/L), and higher than in dairy cow milk (<2 μg/L) [97] and infant formula milk powder (<0.5 μg/g) [98]. However, there is consensus that the benefits of breastmilk for infant outweigh any risk of mercury exposure [95,99-101].

The lactational exposure of infants to MeHg, a developmental neurotoxin [83,102,103], is reduced to ~50% at 2-3 mths of age compared to that expected on the basis of maternal blood levels [49,104]. During this early growth period, infant body weight gains rapidly (~1.5-2x) and the resulting increase in body volume appears to dilute MeHg levels (and lower toxicity) in breastfed infants.

While fish provide healthful dietary proteins and nutrients, such as omega-3 long-chain PUFAs (e.g., DHA and AA) [92,105,106], these benefits may be offset by MeHg contaminant [107-109]. Fish contain 90%-95% of its total mercury as MeHg [110-112]. The EPA RfD for chronic MeHg exposure from diet is 0.7 μg/ kg bw/wk (=mercury in blood, 5.8 μg/L and scalp hair,1.0 μg/g) for optimal health [113]. The provisional TWI of MeHg set by various regulatory agencies is 0.7-1.6 μg/kg bw [108,114]. However, in Japan where fish consumption is highest in the world, TWI for MeHg is 2.0 μg/kg bw [115] and its weekly average lactational exposure in infants is 0.63 μg/kg bw [11]. In 17 EU counties, mothers who consumed at least one fish meal/wk had hair mercury level ≤ 0.55 μg/g with about half of that in their children’s hair [113]. In contrast, the Taiwanese infants have elevated mercury level (79 ng/g stool) at birth due to high maternal intake of mercury (>100 μg/mo.) from fish diet during pregnancy [117,118].

DHA and child development

DHA is considered a critical nutrient in the development of nervous system and infant growth in the early life during gestation and while breastfed [76,105,119-126]. Both FDA and EPA recommend nursing, pregnant and childbearing-age women to consume twice a week seafood containing low MeHg and high DHA levels (e.g., shrimp, pink salmon, seabass, mackerel, whiting, sole, pomfret and trout), and avoid those with low DHA and high MeHg (e.g., whales, swordfish, shark, tuna, halibut, walleye, burbot and pike) [127-130]. Also, AAP, American Heart Association and American College of Cardiology recommend 200-300 mg DHA/day or 1-2 servings of fish/wk [131,132]. A Belgian study found such fish consumption to be safe for increasing the maternal DHA intake [133].

Worldwide human breast milk analysis found a wide range for DHA content (0.06%-1.40%) by wt.; optimal, 0.2-0.5%) with highest concentrations in seafood-consuming coastal populations [134]. Thus, breastfed children of mothers in Menorca, Spain with fish intake >2-3 times/wk during pregnancy (particularly during the third semester spurt of fetal brain development) and lactation achieved significantly higher MSCA scores when tested at age 4 yr. [135]. Additional studies also support such beneficial effects of breast milk DHA in children attributable to maternal fish consumption [136-138]. In the US, only ~25% of pregnant women consume the recommended quantity of fish needed to achieve DHA intake for optimal child health [139].

Since breastmilk DHA levels decrease during 12 wks postpartum, its supplementation is suggested for nursing mothers [140,141]. Thus, DHA supplement via maternal cod fish intake (twice a wk) has enhanced infant development [142- 145]. Also, fish oil supplement has enhanced breastmilk DHA levels in nursing Australian women and development of their children (based on Griffiths score) [146]. Further, the longrange (at 2-4 yr.) developmental benefits of maternal DHA and fish oil supplements have been confirmed by an analysis of 34 clinical trials involving >16,000 breastfed infants [147]. Such supplementation is endorsed in EU [148] and Asia [149]. Nevertheless, studies in India [150], Italy [151] and Netherlands [152] have reported no such benefits of maternal DHA supplementation or fish consumption on child development in the short range (at 1-1.5 yr.).

Prenatal MeHg exposure

While moderate fish intake (1-3 times/wk; recommended by FDA and EPA) during pregnancy improves the metabolic health and inflammatory biomarkers in children, such intake >3 times/wk could lead to unfavorable metabolic profiles [153]. A study of the 14-yr.-old children in the Faroe Islands found an association between CPT (a measure of the speed of visual information processing) and high prenatal MeHg exposure from fish consumption during pregnancy (maternal hair mercury >10 μg/g) [154]. This was attributed to MeHg-induced dysfunction in the brain frontal lobes. Also, the survey of a large group of 44,824 Danish pregnant women with high consumption (60 g/day) of fatty fish (e.g., salmon, trout and halibut) reported reduced fetal growth [155]. However, this study down played the role of MeHg and ascribed the results to other persistent organic pollutants in fish.

The Inuit children of high-fish consuming women in Arctic Quebec, Canada with cord blood mercury >7.5 μg/L were found to be 4x as likely to have IQ<80, the clinical cut-off score for borderline intellectual disability [156].

Interestingly, an analysis of MeHg in 130 placentas at birth in Kuopio University Hospital, Finland found higher amounts in primiparas (first time mothers) which increased with maternal age [76]. A study in Krakow, Poland found that the prenatal exposure to mercury (mean blood levels, maternal >0.5 μg/L and umbilical cord, 1.05 μg/L) from fish consumption, especially during the last trimester of pregnancy, delayed cognitive and psychomotor functions (using BSID scale) in 1-yr-old infants [157,158]. Other factors such as mother’s age, country of origin, smoking and season of delivery were also significantly and independently associated with cord blood mercury concentrations [159]. An additional study found that smoking accelerated the loss of brain neurotrophic factor in newborn induced by maternal MeHg intake from whale diet [160].

In Mexico City, mercury levels in pregnant women (3.4 μg/L blood and 0.5 μg/g scalp hair) and children (1.8 μg/L blood and 0.6 μg/g scalp hair) have been reported [161] These mercury levels are 3-5x higher than those in the US and Canada primarily due to the consumption of seafood contaminated with mercury >EPA guidance value, 0.3 μg/g.

While prenatal mercury exposure is associated with greater risk of ADHD-related behaviors in children, fish consumption during pregnancy appears to provide protection against such behaviors [162-169]. There is ongoing discussion on the adverse effects of maternal mercury exposure on fertility, reproductive health and pregnancy outcomes [74,170]. Based on current evidence, dietary mercury exposure during pregnancy (blood range, 0.64-3.71 μg/L and hair levels, 0.3-5.7 μg/g) is unlikely to be a risk factor for neurodevelopmental deficits in early childhood (0-5 yr.) [171]. In this context, the potential study bias [172] and difficulties in drawing definitive conclusions using neurophysiological tests in children exposed in utero to low levels of MeHg [173] are worth noting. (See Effect of dietary constituents... section below).

Genetics of prenatal MeHg exposure

The genetic predisposition of prenatal MeHg exposure on cognitive deficits (based on WISC-III) in 8-yr-old school children in Bristol, UK has been documented [174]. Also, a prospective study of 2-yr-old Taiwanese children suggested that variants of apoprotein E, a major protein transporter of mercury in the brain, may modify neurodevelopmental effects of MeHg [175]. Additional studies have confirmed that genetic factors can influence mercury toxicity [12,176-179]. Toxicogenomic is now being utilized as an analytical tool to detect mercury in seafood [180].

Prenatal MeHg exposure and heart disease

Regarding the question of whether prenatal MeHg exposure from fish consumption affects blood pressure in children, a study of 12 and 15 yr. old from the Seychelles Islands found no definitive correlation [181], However, similar 14 yr. study of the Faroe Islands birth cohorts observed decreased blood pressure attributable to MeHg neurotoxicity [182].

Several studies have concluded that MeHg from fish consumption may be a potential risk factor for CHD [22,183-186]. Such risk increases when the hair mercury concentration reaches ≤ 2 μg/g [187]. Nevertheless, no association between mercury level and risk of CHD was observed based on toenail analysis in the US, EU and Israel [188,189].

Two recent meta-analysis of fish consumption data noted 60g fish/d as the ideal dose for preventing CHD mortality [190]. Further, higher consumption of fish (≥ 4x/wk) has been associated with greater protection against CHD [191]. The daily fish intake of 60 g happens to be the average consumed by the Japanese who are the highest fish consumers in the world. An earlier analysis of 8 studies of fish consumers (>once/wk) found 17% reduction in CHD [192].

From consumption of MeHg contaminated other dietary constituents by mothers

Among the other dietary constituents besides fish, a Swedish study of pregnant women found that consumption of chicken increased cord blood MeHg levels [193]. Apparently, mercury in chicken originated from fishmeal used as chicken feed.

In high-rice consuming countries, such as China, India and Indonesia, rice is an important dietary contributor of MeHg [45,194,195]. Methylation of mercury in paddy soil, sediments and water used to grow rice plant appears to be the source of MeHg in rice [196]. In China, rice may contain ≤ 569 μg of total mercury/kg, of which ≤ 145 μg/kg is MeHg [197]. The Chinese rice contains higher mercury levels than those grown in other Asian countries [198]. Rice seed has high accumulation potential for MeHg but not for inorganic mercury [199,200]. Notably, there is no significant difference in MeHg concentrations in brown and white (polished) rice since it accumulates primarily in the endosperm [201].

Thus, in inland China, rice rather than fish is the major source of MeHg exposure [202,203]. Stable mercury isotopes (199Hg and 202Hg) in scalp hair can be used to distinguish MeHg intake from rice vs. fish [204]. Compared to fish, rice has lower nutritional value and it lacks micronutrients, such as DHA and Se [205].

The recent survey of pregnant Chinese women found cord blood mercury levels (mean 2.26 μg/L) lower than the WHO/ FAO recommended safe level (8.6 μg/L) [206]. Also, the latest rural Chinese child neurodevelopment study (based on BSID-II MDI and PDI) reported that contemporary changes in family structure had impacted children’s sensitivity to maternal MeHg exposure [202].

Incidentally, the Chinese international rice trade has significantly aggravated MeHg exposures in Africa (62%), Central Asia (98%) and Europe (42%) [27]. Additionally, vegetables, such as cabbage, celery, spinach, pumpkin and amaranthus [207-210], and mushrooms [211] grown in mercury-contaminated soil and water have increased dietary mercury contribution (>FAO/ WHO safe level). However, such mercury contamination can be mitigated by washing produce with water [212] or household vinegar [213].

From consumption of mercury contaminated fish and other dietary constituents by children

Ocean fish consumption is important for the health and development of children in many parts of the world [170,214]. The potential adverse effect of MeHg from contaminated fish consumption on children’s IQ is being debated [156,215,216]. The amount of MeHg ingested depends on: 1) fish species, size, where and which season it was caught, 2) frequency of consumption, and 3) serving size (usually ~70 g/child) [129,130,217].

An advisory limit of 1 μg MeHg/g fish has been set by FDA [218]. The EPA threshold mercury dose for neurodevelopmental effects from fish consumption is 0.1 μg/kg bw/d [218]. Suggested weekly consumption quantities of DHA-rich fish (salmon, sardines, Atlantic mackerel, etc.) for children are: ages 5-11 yr. (average bw 14.4 kg), 40 g and ages 5-11 yr. (average bw 26.4 kg), 74 g with monthly limits for larger predatory fish (whales, shark, tuna, etc.) for 1-4 yr., 75 g and 5-11 yr., 125 g [219,220]. A recent survey of US children found blood mercury levels <EPA RfD (5.8 μg/L) in 1-19 old [58] with no adverse effect on adaptive and problem behaviors (based on BASC-2 scores) [221].

The desirable mercury level in scalp hair of fish-consuming children is <2.3 μg/g (WHO reference value) [222]. The form of fish consumed (fresh, frozen or canned) or how it is cooked (baked, grilled or pan/deep fried) generally does not affect its mercury content [223]. Since MeHg in fish has already bound to tissue proteins [73], it is not eliminated by cleaning or cooking [176]. However, acidic medium (e.g., vinegar) can release mercury bound to fish proteins [224].

Based on VEP measurements in children, the Canadians have recommended the total blood mercury threshold limit of 8 μg/L for pregnant and childbearing-age women [225,226]. Among the Inuit population of Nunavik in Northern Quebec, staple diet of fish and marine mammals has resulted in higher mercury levels in blood and scalp hair of their children, the former correlating with neuromotor functions [227-229]. Similar results have also been reported in the Arctic populations [25].

EU has adopted the EPA RfD for MeHg exposure [230]. Studies of mother/child pairs in Ireland found scalp hair mercury levels<1.0 μg/g [231] and in the Italian coastal population of the Mediterranean Sea (which borders 21 countries), the MeHg levels from fish consumption were <TWI recommended by EFSA (1.3 μg/kg bw) [232]. In contrast, children in Spain (Granada, Madrid, Murcia, the Ribera d’Ebre and Menorca Island) have higher levels of MeHg in scalp hair [233-235]. Their consumption of oily and canned fish positively correlated with cognitive functions (based on MSCA scores) and negatively with white fish (bass, catfish, cod, tilapia, etc.) intake, especially when fried.

The biomonitoring studies of mercury in the Japanese children found no adverse effects on neurodevelopment (BAEP test) or scholastic achievement (SACMEQ test) attributable to fish consumption [79,236]. The reference level for mercury in scalp hair in Japan, the world’s largest fish consumer, is 3 μg/g based on TWI of 2.0 μg mercury/kg bw from fish.

Although Jamaican children consume large amounts of seafood and their blood mercury levels are much higher (0.99 μg/L) than those in the US and Canadian children (0.33 and 0.31 μg/L, respectively), no association between blood mercury levels and ASD was observed [237]. This paper discusses discrepancies in earlier studies that reported such association. A study with US children has also affirmed this conclusion [238].

The Chinese use fish congee as weening food for toddlers which may contain 50-520 μg mercury/kg depending on the type of fish used. This can result in the child’s weekly intake of 1.2-13.0 μg mercury/kg bw. The infants fed such congee exceeding TWI of MeHg (1.6 μg/kg bw) have exhibited neurological and other symptoms of mercury poisoning [239]. Also, the fish-consuming Chinese children in Hong Kong have blood mercury level >5.82 μg/L with >9x higher risk of exhibiting ADHD [240].

In Australia, children’s diet does not contain the recommended amounts of PUFAs, especially DHA since they consume 8.5x more meat than fish and seafood [241]. However, the high consumption of vegetables appears to help increase their total dietary PUFA intake [242,243]. Currently, infant formulas supplemented with DHA are popular in Australia [244]. The later-life benefits of DHA on neurodevelopment [245,246] and cardiovascular function [247] are the reasons for its supplementation.

The 2013 survey of 168 baby foods sold in the US found that 32% contained <0.146-4.060 μg/kg of total mercury with those containing rice topping the list [248]. Also, marlin fish jerky snack food popular with children in Hawaii and California contains high concentrations of mercury (average 5.53 μg/g) [249]. The recent US congressional report found up to 10 μg/kg mercury in some US made baby foods [250]. FDA has proposed a 4-yr. “Closer to Zero Action Plan” for baby food toxic metal contaminants which includes mercury [251].

Mercury-contaminated fish consumption pattern around the world

Like rest of the world, fish consumption in the US is the primary way the women of childbearing age and their children are exposed to MeHg, and it is generally below the level of any health concern [252]. Even so, according to the NHNE survey of 1999-2000, >300,00 newborns each yr. may have been exposed in utero to MeHg levels >EPA RfD [253]. Also, high fish consumption among women of reproductive age, especially African and Asian Americans, has resulted in preterm births in Maryland, South Carolina, Louisiana and Florida [254-258] with potential lower childhood IQ [156].

The 2008-2009 EPA survey of 541 sites across the continental US found mean mercury concentrations of 21-1,419 μg/kg fish [259]. The 2009-2012 survey of 5,656 US children ages 1-19 yr. found that 62.4% ate fish and had blood mercury levels below the EPA reference level, 5.8 μg/L [260]. An earlier survey of 1-5 yr. old children had also reported the historically lowest blood MeHg and total mercury concentrations (0.17 and 0.26 μg/L, respectively) [261]. However, the San Francisco Bay area children in California are known to be high-end fish consumers with elevated blood mercury levels [109]. Additionally, American children in Alaska and Hawaii have higher amounts of fish in their diet.

The fish consumption pattern in 17 EU countries has been studied [117]. The Portuguese are third largest fish consumers in the world, after Japan and Iceland. A survey of 343 pregnant women in Lisbon found their mean RI for MeHg exposure from fish consumption to be 0.81 (calculated by fish intake in μg/ kg bw/d ÷ 0.24 μg/kg bw/d, the WHO tolerable daily intake; the desired RI <1.0) [262]. Notably, the ingestion of black and silver scabbard fish enhanced mercury toxicity risk [263].

The 2015 Spanish consensus document on the prevention of MeHg exposure has recommended that pregnant and nursing women as well as children should consume fish containing mercury levels <0.15 mg/kg, (resulting blood levels of ~10.8 μg MeHg/L and ~12 μg total mercury/L) [217]. This is comparable to the Japanese (who consume more fish per capita) but higher than those in the US, Canada and other EU countries.

In South America, an analysis of 110 species of fish from Madeira River, the biggest tributary of Amazon in Brazil found a concentration range of 0.01-6.06 μg mercury/g [264]. Among the high fish-eating villagers (~406 g/d), mean scalp hairmercury level (17.4 μg/g) of breastfeeding mothers significantly correlated with their children’s hair level [265,266]. While this had no significant impact on newborn birthweight [267], impairment in motor performance (TGMD-2 test) was observed at ages 7-11 yrs. [268]. However, such developmental delays were also attributable to their health inequalities and socioeconomic disadvantages [96].

The children with fish as the main component of their diet (283 g/day containing ≤ 0.2 μg mercury/g) in the fishing communities along the Caribbean coast of Colombia are potentially exposed to MeHg 3x WHO/FAO TWI, 1.6 μg/kg bw [269]. Similarly, the children living in the northern border area are exposed to high levels of MeHg from consumption of fish from rivers polluted by mercury-containing wastewater from the artisanal gold mines [270].

West Bengal is a high fish consuming state in India with a population of >10 million children of age ≤ 6 yr. The 2016 analysis of scalp hair of younger residents (<21 yr.) of a fishing community near Kolkata, the state capital found mean total mercury value less than EPA RfD (1.0 μg/g) [271]. The city residents had lower hair mercury level (0.49 μg/g) compared to those from the fishing community (0.83 μg/g), presumably due to lower fish consumption. Also, recent surveys of commercial fish from the Bay of Bengal [272], coastal Mumbai [273] and Goa, another high fish consuming region [274], found mercury levels within the permissible limits.

Over the past five decades (1961-2011), there has been a worldwide increase in human exposure to MeHg from fish consumption (>TWI 1.6 μg/kg bw) [275]. The annual health benefits of a 10% reduction in MeHg exposure in the fish-consuming US population is estimated to be $860 million [276]. Of this, 80% is associated with reduction in fatal heart attacks and 20% in IQ gains in children. EFSA [277] has recommended that each country needs to consider its own pattern of fish consumption for risk-benefit analysis. Sushi fans should note that raw fish may contain 55%-60% more bioaccessible mercury than in cooked or fried ones [278,279].

Reports of biomonitoring and risk assessment of mercury contamination in fish from various parts of the world are available [280-282]. Also, there is a compilation of mercury content of vegetables, fruits and fish consumed in India which, in general, is within TWI [283].

A field experiment in France found that risk-benefit advisory had minimal effect on consumer fish choice [284]. Instead, store warning labels on fish with high mercury content were recommended as a more effective tool. In the US, consumer advisories also have no major impact on fish choices made by the women of childbearing age [285-287].

Thus, both maternal and children’s consumption of mercury contaminated fish and other dietary constituents continue to be of active research interest around the world.

Mercury vapor exposure from mercury-containing devices

Mercury is the only element that is liquid at room temperature, 13.6x heavier than water and readily evaporates. One 4-mm diameter bead of mercury (0.034 ml or 0.46 g) can generate at 0.1 m above ground, up to 0.56 μg mercury vapor/m³ of room air in 30 min at 170^oC. This vaporization increases rapidly as temperature rises, e.g., ~6x at 38^oC [288].

Since mercury vapor is colorless and odorless, its detection in home could be challenging without professional help. If concentrations >1 μg mercury/m³ room air are detected, cleanup should be initiated and residents evaluated for exposure [289]. Their relocation is called for when the mercury reaches toxic level of ≥ 10 μg/m³ room air [290-292].

The most common cause of mercury vapor exposure of children at home is due to broken fever thermometers, blood pressure monitors and light bulbs. Although spills from broken thermometers (which contain 0.5-0.7 g mercury) rarely reach mercury vapor levels >1 μg/m³ room air [43,64,292]. they could create hazardous conditions to infants if such indoor spills are improperly cleaned (See Clinical signs, etc. section below). In contrast, blood pressure monitors contain larger amount of mercury (~150 g) and when broken, they are more likely to create a hazardous situation, as in the case of a home day care center in Hillsborough County, Florida. Unknowingly it utilized a leaking antique monitor (resulting in ≤ 89 μg mercury/m³ room air) as an educational toy [293]. Also, a recent mercury spill entered HVAC system in the basement of a house in Virginia exposing a family with 3 children to toxic vapors [294].

Since spilled mercury disperses into small droplets that get embedded in carpet fibers and floor cracks, vacuum cleaning produces aerosols and enhances its vaporization. Thus, the recent attempt to vacuum clean a spill of ~40 g of mercury from a broken barometer in a Netherland home resulted in high blood levels (26-32 μg/L) in a boy (9 mos.) and his sister (2.5 yrs.) within 6 h of exposure [295]. Similar poisoning of children in the US attributed to vacuum cleaning of mercury spills from broken thermometers has been reported [67]. Hence, vacuuming or using broom to clean mercury spill is not recommended [289]. Poor ventilation and elevated temperatures further increase mercury levels in the room air. Activated alumina may be used to cover-up inaccessible mercury spillage to reduce vaporization [9]. Mercury spills larger than that from a broken thermometer need to be promptly remediated by professionals [296,297]. A review of health consequences of mercury spills from common devices at home is available [44]. Most countries have mercury emergency phone hot lines. In the US, it is 800-220-1222 at the Poison Control Center.

ln contrast, the widely-used 4-ft long fluorescent tube lights contain smaller amounts of elemental mercury vapor (12-20 mg) and only 6% of this is released to the air when broken. Notably, mercury binds to glass as the bulb ages and ~4 mg is oxidized [298]. The compact FLBs contain even smaller amounts of mercury vapor (3.0-4.5 mg). Thus, mercury hazard from broken light bulbs in homes is minimal. In most instances, the small amount of mercury released can be adequately vented by opening windows and using exhaust fans to achieve the EPA reference level (≤ 0.3 μg/m³) [289].

In the rare instances of broken fever thermometers in the mouth of young children, as recently reported in Shanghai, China, X-ray images can help locate mercury residue and in one child, local excision was resorted to remove it from the floor of mouth [299]. Accidental ingestion of mercury from a broken thermometer is generally non-hazardous due to its poor absorption in the oral cavity and GI tract [8]. There is a recent report of mercury in the vomitus after drinking milk spiked with the metal [300]. Similarly, absorption of elemental mercury through skin contact is low (0.024 ng/m² for each mg/m³ room air) [61].

Exposure from heating mercury to extract gold and silver from ores and scrap

Extraction of gold and silver from ores by mercury amalgamation and from scrap dental fillings involves heating which could generate potentially lethal concentrations of vaporized mercury (0.193-0.370 mg/m³ room air). Such operations at home by amateurs, especially in the poorly ventilated residential kitchens have resulted in children’s death [301,302]. Also, fetal uptake of mercury could take place in exposed pregnant women due to its facile transfer across the placenta [303]. (See Clinical signs, etc. section below).

To avid entrepreneurs, there is good news of the availability of a mercury-free gold extraction procedure which uses Borax (sodium borate), a common ingredient of household cleaners and laundry detergents [304].

Exposure from cultural or religious ceremonial uses of mercury

Some Caribbean and Latin American religions, such as Voodoo, Santeria, Palo and Espiritismo use mercury ceremonially and apply it to the skin, add to candles or sprinkle around the house [46,55,303,305]. As a precaution, homes of these religious practitioners should be monitored to assure mercury levels are <1.0 μg/m³ room air. Also, blood, urine and scalp hair levels of mercury should be checked in young children suspected of such ritualistic exposures [306].

Exposure from unregulated cosmetics, herbal medicines, dietary supplements, toys and jewelry

Chloride and bromide salts of mercury are commonly used in cosmetics, herbal medicines and dietary supplements [307]. The 2003 FDA list of mercury containing medicinal products is still of current relevance due to their continued popularity [308]. Also, low-cost jewelry and toys from Mexico and Asian countries are often contaminated with mercury [309-311].

Parents and other family members use of facial skin-lightening creams containing mercury salts (which inhibit melanin formation) may expose children to the toxic metal [66,312- 316]. Also, mercurous chloride (calomel) in teething powder is known to cause childhood mercury poisoning (acrodynia or pink disease, see Clinical signs, etc. section below).

Herbal medications sold OTC in pharmacies and via the internet are often contaminated with mercury (some as high as 103 mg/g). Also, mercury concentrations >4.2 mg/g in herbal dietary supplements are not uncommon, with bamboo shoots and green microalga being the frequent contributing ingredients [317,318]. However, mercury in traditional Ayurvedic medicinal products from India is generally not a contaminant but added as an active ingredient [319]. Mercury poisoning of children in the US and EU by such medications has been reported [320].

Moreover, herbal teas could be a significant source of mercury exposure in children [321]. (AAP recommends not to feed infants herbal teas (which may also contain other toxins, such as pennyroyal oil in mint tea) which could lead to fatalities [322].

In the US, FDA (per 21CFR700.13) has approved the use of mercury compounds as preservative in eye products only (at ≤ 65 μg/g) [308]. Thus, all cosmetics containing mercury >1 μg/g. with the exception of eye products, are considered contaminated and subject to regulatory action.

Exposure from workplace tracking of mercury to homes

Elevated levels of mercury in children and homes of workers of plants manufacturing thermometer, FLB and chlor-alkali products have been reported [299,323,324]. Thus, in the US, the urine mercury level was higher (25 μg/L) in the children of a Vermont thermometer plant workers than those of non-mercury plant workers (5 μg/L) [324]. Also, mercury contamination in homes of a chlor-alkali plant workers in Charleston, Tennessee during scheduled maintenance has been reported [323]. Although no toxic effects were observed in both cases, the children of mercury plant workers are potentially at risk and monitoring is advised. Additionally, it is prudent for the plant workers to wear separate work clothes and shoes to prevent carrying mercury contamination outside of the work area [9].

Workplace tracking of mercury from clinic to home by dental professionals who work with mercury containing amalgam fillings is considered not significant because of the relatively small quantities of the metal they handle. (See Exposure to mercury used in dentistry section below).

A recent indoor air mercury monitoring in ten hospitals in Bali, Indonesia found that 90% of the hospital area had <1 μg/m³, 9% 1-10 μg/m³ and 1% >10 μg/m³ with higher concentrations in emergency rooms and dental clinics, and the highest in equipment repair/maintenance workshops [325].

Exposure from industries that use mercury near homes

Chlor-alkali plants produce chlorine, hydrochloric acid, caustic soda (sodium hydroxide) etc., using mercury cells each containing about 8,000 lb of mercury. A typical plant uses about 56 such cells [326]. Elevated levels of MeHg in water (7 ng/L) and fish (5.2 mg/kg) in a Romanian reservoir due to microbial methylation of mercury released from a chlor-alkali plant have been documented [327]. Similarly, leafy vegetables grown near a chlor-alkali plant in Ganjam, Odisha State, India contained elevated mercury levels (8.9 mg/kg) [328]. Also, higher atmospheric levels of mercury (27.4 μg/m3 air) in the vicinity of chlor-alkali plant in Flix, Spain are reported [329]. The scalp hair MeHg analysis of 4-yr. old children living near this plant found twice the amount (0.631 μg/g) compared to those not living near the plant [330]. However, their hair mercury levels decreased over the 13-yr. period with no correlation with neurophysiological test scores (TMT-B and FTT) and ADHD [331]. Similar results were obtained in the vicinity of a chloralkali plant in Portugal shut down after 50 yr. of operation [332]. Further, a detailed study of ambient air, soil and vegetables grown in the vicinity of a chlor-alkali plant in Tuscany, Italy found mercury concentrations within the EU safe level [333].

In 2014, there were an estimated 50 chlor-alkali plants around the world and in the US, just 2 as of 2018 [334]. The environmental exposure hazards to children are minimal from other industries that use smaller quantities of mercury (e.g., thermometer and FLB manufacturers). An exception was a USowned thermometer factory in Kodaikanal, Tamil Nadu, India. It was shut down for blatantly polluting the pristine environment of the popular hill station by discharging waste mercury in the early 2000s [335].

Mercury exposure at schools

Students are attracted to silvery liquid mercury which disperses into tiny droplets and quickly forms large globs upon shaking or scooping with fingers [336]. The common sources of mercury vapor exposure at school are: 1) elemental mercury stored in science laboratories, 2) mercury from broken instruments and FLBs, and 3) gymnasium floors covered with certain polyurethane material (such as 3M Tartan) manufactured prior to 1985 using mercury-containing catalyst [61,310].

Student misuse of mercury accounts for numerous short-term exposures to its vapor as reported in Arizona, Mississippi, Missouri, Nevada, Texas and Washington, DC schools in the US [68,337-339]. Thus, mercury stolen from storage rooms was taken to class rooms, gym and homes. The air mercury levels measured were highest near the student locker rooms (50 μg/m³ compared to the background, 0.01-0.04 μg/m³). The mean urine mercury level of 200 students tested was 0.36 μg/L (range 0.14- 11.4 μg/L) with higher levels in those touched mercury and/ or got it on their clothes. One school was closed for 35 days for cleanup and over 200 homes were tested for contamination. In the most recent incident, a high school in Chicago, Illinois was evacuated after the discovery of mercury in bathroom toilet (Chicago Tribune, Jan 14, 2023).

In general, there have been not many reports of severe adverse effects in students that required medical attention due to mercury exposures in the US schools [337]. In 2020, three students in Dallas, Texas developed symptomatic elemental mercury poisoning that required hospitalization and chelation therapy with DMSA [68].

Besides the US, in the past 10 yrs. many students in Turkey were poisoned by mercury in several schools [69,340-342]. Over 250 children were exposed by unauthorized handling of mercury and in one case, 26 were intoxicated as the result of a broken mercury thermometer in a hot, closed-door laboratory. These acute mercury vapor exposures were detected early on and successfully treated with D-penicillamine or N-acetyl cysteine.

A mercury awareness guide for school teachers is available [343]. The acceptable level of mercury in indoor air for school is 1-3 μg/m³ which is higher than that for home (<1 μg/m³) accounting for less time spent in school by children [344].

Mercury exposure at other locations

In the US, children’s exposu